Is Unplanned PICU Readmission a Proper Quality Indicator? A Systematic Review and Meta-analysis.

CONTEXT: Unplanned PICU readmissions within 48 hours of discharge (to home or a different hospital setting) are considered a quality metric of critical care. OBJECTIVE: We sought to determine identifiable risk factors associated with early unplanned PICU readmissions. DATA SOURCES: A comprehensive search of Medline, Embase, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to July 16, 2018. STUDY SELECTION: Observational studies of early unplanned PICU readmissions (<48 hours) in children (<18 years of age) published in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently and abstracted data. A meta-analysis was performed by using the random-effects model. RESULTS: We included 11 observational studies in which 128 974 children (mean age: 5 years) were evaluated. The presence of complex chronic diseases (odds ratio 2.42; 95% confidence interval 1.06 to 5.55; I 2 79.90%) and moderate to severe disability (odds ratio 2.85; 95% confidence interval 2.40 to 3.40; I 2 11.20%) had the highest odds of early unplanned PICU readmission. Other significant risk factors included an unplanned index admission, initial admission to a general medical ward, spring season, respiratory diagnoses, and longer initial PICU stay. Readmission was less likely after trauma- and surgery-related index admissions, after direct admission from home, or during the summer season. Modifiable risk factors, such as evening or weekend discharge, revealed no statistically significant association. Included studies were retrospective, which limited our ability to account for all potential confounders and establish causality. CONCLUSIONS: Many risk factors for early unplanned PICU readmission are not modifiable, which brings into question the usefulness of this quality measure.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit.

OBJECTIVE: We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. STUDY DESIGN AND SETTING: We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. RESULTS: We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1-13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). CONCLUSION: About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Assessing the evidence: live attenuated influenza vaccine in children younger than 2 years. A systematic review.

BACKGROUND: Live attenuated influenza vaccine (LAIV) is effective in children but contraindicated in children <2 years of age. METHODS: We searched Medline, EMBASE, the Cochrane Library, Web of Science, Scopus, PsycInfo and CINAHL through February 2013 for existing systematic reviews, randomized controlled trials (RCTs) and observational studies (for safety). We included studies enrolling healthy children <2 years of age who received LAIV, compared with placebo or inactivated influenza vaccine (IIV). Data were extracted independently by 2 investigators. The relative risk (RR) was pooled across studies using the random effects model. RESULTS: We found 7 eligible randomized controlled trials and 2 observational studies. Randomized controlled trials included 6281 children and were at low to moderate risk of bias. LAIV reduced the incidence of influenza compared with placebo (relative risk = 0.36, 95% confidence interval: 0.23-0.58, P < 0.05) with a number needed to vaccinate of 17. LAIV increased the incidence of minor side effects (fever and rhinorrhea). LAIV had a similar effect in preventing influenza (relative risk = 0.76, 95% confidence interval: 0.45-1.30, P > 0.05) compared with inactivated influenza vaccine. There was an increase of hospitalization rate (post hoc analysis) and medical attended wheezing with LAIV. CONCLUSIONS: LAIV is highly effective in children <2 years of age compared with placebo and is as effective to inactivated influenza vaccine. The safety profile of LAIV is reasonable although evidence is sparse. LAIV may be considered as an option in this age group particularly during seasons with vaccine shortage.

Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review.

BACKGROUND: Poor fidelity to practice guidelines in the care of people with multiple chronic conditions (MCC) may result from patients and clinicians struggling to apply recommendations that do not consider the interplay of MCC, socio-personal context, and patient preferences. OBJECTIVE: The objective of the study was to assess the quality of guideline development and the extent to which guidelines take into account 3 important factors: the impact of MCC, patients' socio-personal contexts, and patients' personal values and preferences. RESEARCH DESIGN: We conducted a systematic search of clinical practice guidelines for patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two reviewers working independently selected studies, extracted data, and evaluated the quality of the guidelines. RESULTS: We found 28 eligible guidelines, which, on average, had major methodological limitations (AGREE II mean score 3.8 of 7, SD=1.6). Patients or methodologists were not included in the guideline development process in 20 (71%) and 24 (86%) guidelines, respectively. There was a complete absence of incorporating the impact of MCC, socio-personal context, and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines, respectively. When mentioned, MCC were considered biologically, but not as contributors of complexity or patient work or as motivation to focus on patient-centered outcomes. CONCLUSIONS: Extant clinical practice guidelines for one chronic disease sometimes consider the context of the patient with that disease, but only do so narrowly. Guideline panels must remove their contextual blinders if they want to practically guide the care of patients with MCC.

Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design.

BACKGROUND: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question. METHODS/DESIGN: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials. DISCUSSION: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

Screening for gestational diabetes: a systematic review and meta-analysis.

CONTEXT: Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycemia with first recognition during pregnancy. The optimal time to screen for GDM that would maximize the yield and benefits remains unclear. OBJECTIVE: Our objective was to appraise the evidence regarding screening for GDM (accuracy, correlation with adverse outcomes, and harms). DATA SOURCES: We searched Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011. STUDY SELECTION: We included randomized controlled trials and observational studies that enrolled pregnant woman who were evaluated using different GDM screening tests. DATA EXTRACTION: Two reviewers working independently abstracted the data. RESULTS: We did not find any randomized controlled trials of GDM screening that measured feto-maternal outcomes. A 1-hour 50-g glucose challenge test with a cutoff point at 140 mg/dL was the most commonly used screening method. The results of this test were statistically associated with feto-maternal outcomes (P < .001), even though only 11% of individuals with a positive test (according to Carpenter and Coustan criteria) developed GDM. Positive Carpenter and Coustan criteria were associated with macrosomia (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.9-3.1, P < .001) and gestational hypertension (OR = 1.7, CI = 1.3-2.1, P < .001). Positive National Diabetes Data Group criteria were also associated with macrosomia (OR = 3.2, CI = 2.3-4.4, P < .001) and gestational hypertension (OR = 2.1, CI = 1.6-2.8, P < .001). CONCLUSIONS: Indirect evidence supports the use of contemporary screening tests for GDM to identify pregnancies at increased risk of adverse feto-maternal outcomes. It also suggests that use of these tests will place some women under unnecessary treatment for GDM.

Glucose targets in pregnant women with diabetes: a systematic review and meta-analysis.

BACKGROUND: Glucose-lowering treatments are used during pregnancy to reduce the risk for complications in the mother and offspring, yet treatment targets have not been established. OBJECTIVE: Our objective was to appraise and summarize the available evidence regarding the association between different blood glucose targets during pregnancy and fetal and maternal outcomes. METHODS: We searched Medline, EMBASE, Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011 for randomized trials and observational studies that enrolled women with diabetes during pregnancy and reported planned or achieved glucose targets. We used random-effects meta-regression models to estimate the odds ratio for the association of outcomes of interest and glucose targets. When possible, we adjusted for diabetes type, trimester, and diabetes treatment. RESULTS: We included 34 studies enrolling 9433 women. The studies had moderate to high risk of bias due to evidence of reporting bias and insufficient adjustment for important covariates, particularly maternal body mass index. A fasting glucose target of <90 mg/dL was the most commonly reported and the one most strongly associated with reduced risk of macrosomia (odds ratio = 0.53, 95% confidence interval = 0.31-0.90, P = .02) for women with gestational diabetes during the third trimester. For type 1 and type 2 diabetes, and for pre- and postprandial targets, data were sparse and inconclusive. CONCLUSIONS: Evidence warranting very low confidence in the estimates suggests that a fasting glucose target of <90 mg/dL is associated with a lower risk of macrosomia and other outcomes of different importance in women with gestational diabetes. Whether this target can be extrapolated to women with pregestational diabetes or whether targets above or below this threshold offer a better benefit/risk balance remains unclear.

Systematic reviews supporting practice guideline recommendations lack protection against bias.

OBJECTIVE: To evaluate the quality of systematic reviews (SRs) affecting clinical practice in endocrinology. STUDY DESIGN AND SETTING: We identified all SRs cited in The Endocrine Society's Clinical Practice Guidelines published between 2006 and January 2012. We evaluated the methodological and reporting quality of the SRs in duplicate using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. We also noted if the guidelines recommendations that are clearly supported by SRs acknowledged their quality. RESULTS: During the 5-year period of study, endocrine guidelines cited 69 SRs. These SRs had a mean AMSTAR score of 6.4 (standard deviation, 2.5) of a maximum score of 11, with scores improving over time. SRs of randomized trials had higher AMSTAR scores than those of observational studies. Low-quality SRs (methodological AMSTAR score 1 or 2 of 5, n = 24, 35%) were cited in 24 different recommendations and were the main evidentiary support for five recommendations, of which only one acknowledged the quality of SRs. CONCLUSION: Few recommendations in endocrinology are supported by SRs. The quality of SRs is suboptimal and is not acknowledged by guideline developers.

Influenza vaccines licensed in the United States in healthy children: a systematic review and network meta-analysis (Protocol).

BACKGROUND: Influenza is an acute respiratory illness caused by influenza viruses, which occurs in epidemics worldwide every year. Children are an important target for prevention methods, including vaccination. While evidence about the decision on whether to vaccinate healthy children is robust, evidence supporting the decision of which of available vaccines to use remains unclear.This review will summarize the evidence about the efficacy and safety of the available vaccines for seasonal influenza licensed in the United States for use in healthy children. METHODS/DESIGN: An umbrella systematic review (SR) and network meta-analysis will be conducted of randomized controlled trials (RCTs). We will search for SRs to identify parallel RCTs evaluating inactive and/or live attenuated influenza vaccines licensed in the United States for use in healthy children to prevent influenza. Subsequently, we will update the literature search of the selected SRs to the present time to capture recent controlled studies. To complement the work focused on harms, we will also select observational studies focusing on post marketing retrospective studies. Inclusion will not be limited by language, publication date or publication status. To identify additional candidate studies, we will review the reference lists of the eligible primary studies and narrative reviews; we will query the expert members of the Advisory Committee on Immunization Practices and review references from their previous statement. Additionally, we will review the reports from the Institute of Medicine on the adverse effects of vaccines. Two reviewers will independently determine study eligibility and will extract descriptive, methodological (using the Cochrane risk of bias tool for RCTs and the Newcastle-Ottawa scale for observational studies) and efficacy data. When possible, we will conduct meta-analyses and network meta-analyses by combining indirect and direct comparisons.We will evaluate heterogeneity using the I2 statistic and the agreement of indirect comparisons and direct evidence. We will report the Cochrane Q test to determine the statistical significance of heterogeneity.The overall quality of evidence will be assessed following the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach. DISCUSSION: Our systematic review will allow patients, clinicians, guideline developers and policy makers to make evidence-based choices between the two available vaccine options, by providing information regarding benefits and harms of these types of vaccines.